Endothelin (ET) is a vasoconstrictor peptide composed of 21 amino acid residues, which was first isolated from a culture supernatant of porcine aortic endothelial cells and characterized (Yanagizawa et al., Nature, 332, 411-415, 1988). Subsequent research suggested that endothelin occurs in at least 3 isoforms (ET-1, ET-2 and ET-3), and two endothelin receptors, ET.sub.A (being concerned with only action of vasoconstriction) and ET.sub.B (being concerned with mainly action of vasodilation), have been identified.
Since the discovery of endothelin, searches for anti-endothelin compounds have been energetically undertaken to develop therapeutic drugs for diseases pathologically associated with endothelin. Results of such exploratory endeavors have been reported in EP-A-552,489, EP-A-528,312, EP-A-499,266, WO 91/13089, EP-A-436,189, EP-A-457,195, EP-A-510,526, WO 92/12991, EP-A-496,452, EP-A-526,708, EP-A-460,679, WO 92/20706, among other reports. The compounds described in the above reports are suggested to be effective as anti-hypertensive agents, therapeutic drugs for cardiovascular/cerebrovascular diseases (such as myocardial infarction), therapeutic drugs for diseases of the kidney, antiasthmatic agents, antiinflammatory agents, and/or antiarthritic agents but there is no specific description about their application as a therapeutic or prophylactic drug for cerebral infarction. On the other hand, EP-A-655,463 describes that a compound which exhibits excellent antagonistic action against endothelin B receptors is useful for diseases caused by endothelin, such as hypertension, cerebral infarction, etc.
In view of the above state of the art, the inventors of the present invention investigated agents of use for the clinically beneficial prevention or treatment of cerebral infarction and firstly found surprisingly that anti-endothelin compounds having specific chemical structure are effective for the purpose, based on concrete data. They accordingly have perfected the present invention.